A series of 2-substituted aminoindenes were synthesized in our laboratories and tested for pharmacological activity. The 2-n-propyl and 2-n-butyl aminoindenes proved to be potent intracellular antagonists of calcium in studies involving excitation-contraction coupling in a variety of smooth muscle preparations and stimulus-secretion coupling in the isolated adrenal medulla. Additional studies demonstrated that the 2-substituted aminoindenes relaxed isolated bovine coronary vessel strips contracted by high potassium. Additionally, these compounds increased coronary flow and decreased cardiac inotropic activity in the isolated perfused rabbit heart preparation. Preliminary investigations demonstrated the antiarrhythmic activity of the 2-substituted aminoindenes in the anesthetized dog rendered arrhythmic by ouabain infusion. The proposed continuation studies of this project involve an in-depth investigation of the antiarrhythmic effect of the aminoindenes against a variety of arrhythmogenic drugs (strophanthidine, calcium, aconitine), as well as establishment of the complete toxicological profile of the compounds. This should pave the way for the synthesis of structural analogues with favorable therapeutic indices.